埃索美拉唑镁usp34标准.pdfVIP

esomeprazole magnesium (es oh mep ra zole mag nee zee um). c34h36mgn6o6s23h2o trihydrate: 767.17 c34h36mgn6o6s2 anhydrous: 713.12 1h- benzimidazole,5- methoxy- 2- (s)- (4- methoxy- 3,5- dimethyl- 2- pyridinyl)methylsulfinyl, magnesium salt (2:1), trihydrate; 5- methoxy- 2- (s)- (4- methoxy- 3,5- dimethyl- 2- pyridyl)methylsulfinylbenzimidazole, magnesium salt (2:1), trihydrate 217087- 09- 7. definition esomeprazole magnesium contains nlt 98.0% and nmt 102.0% of c34h36mgn6o6s2, calculated on the anhydrous basis. identification a. infrared absorption 197k b. the sample solution, prepared and tested as directed in the test for content of magnesium, exhibits a significant absorption at 285.2 nm. assay procedure solution a: dissolve 0.725 g of monobasic sodium phosphate and 4.472 g of anhydrous dibasic sodium phosphate in 300 ml of water, and dilute with water to 1000 ml. dilute 250 ml of this solution with water to 1000 ml. if necessary, adjust with phosphoric acid to a ph of 7.6. solution b: mix 11 ml of 0.25 m tribasic sodium phosphate with 22 ml of 0.5 m dibasic sodium phosphate, and dilute with water to 100 ml. mobile phase: acetonitrile and solution a (7:13) standard solution: transfer 10 mg of usp omeprazole rs to a 200- ml volumetric flask, and dissolve in about 10 ml of methanol. add 10 ml of solution b, and dilute with water to volume. notethis solution contains 0.05 mg/ml of omeprazole. sample solution: transfer 10 mg of esomeprazole magnesium to a 200- ml volumetric flask, and dissolve in about 10 ml of methanol. add 10 ml of solution b, 页码，1 / 7 2 0 1 0 u s p c o f f i c i a l 5 / 1 / 1 1 - 7 / 3 1 / 1 1 u s p m o n o g r a p h s : e s o m e p r a z o l e . . . 2 0 1 1 - 5 - 4f i l e : / / c : c o m _ c a i s l a b s _ e b k d a t a v 3 4 2 9 0 u s p 3 4 n f 2 9 s 0 _ m 3 0 5 8 8 . h t m l and dilute with water to volume. notethis solution contains 0.05 mg/ml of esomeprazole magnesium. chromatographic system (see chromatography 621 , system suitability.) mode: lc detector: uv 280 nm column: 4.0- mm 12.5- cm or a 4.6- mm 15- cm; 5- m packing l7. note alternatively, a 3.9- mm 15- cm column that contains 4- m packing l1 may be used. flow rate: 1 ml/min injection size: 20 l system suitability sample: standard solution suitability requirements column efficiency: nlt 2000 theoretical plates relative standard deviation: nmt 2.0% analysis samples: standard solution and sample solution calculate the percentage of c34h36mgn6o6s2 in the portion of esomeprazole magnesium taken: result = (ru/rs) (cs/cu) mr1/(2 mr2) 100 acceptance criteria: 98.0%102.0% on the anhydrous basis other components content of magnesium lanthanum solution: transfer 58.7 g of lanthanum oxide into a 1000- ml volumetric flask, wet the substance with some water, and dissolve by cautious addition of 250 ml of hydrochloric acid in 20- to 30- ml portions, cooling between the additions. add water while stirring, cool to room temperature, and dilute with water to volume. notestore the solution in a plastic bottle. standard stock solution: 1000 g/ml of magnesium in water, from a commercially ru= = peak response from the sample solution rs= = peak response from the standard solution cs= = concentration of omeprazole in the standard solution (mg/ml) cu= = concentration of esomeprazole magnesium in the sample solution (mg/ml) mr1= = molecular weight of esomeprazole magnesium, 713.12 mr2= = molecular weight of omeprazole, 345.42 页码，2 / 7 2 0 1 0 u s p c o f f i c i a l 5 / 1 / 1 1 - 7 / 3 1 / 1 1 u s p m o n o g r a p h s : e s o m e p r a z o l e . . . 2 0 1 1 - 5 - 4f i l e : / / c : c o m _ c a i s l a b s _ e b k d a t a v 3 4 2 9 0 u s p 3 4 n f 2 9 s 0 _ m 3 0 5 8 8 . h t m l prepared atomic absorption standard solution. notestore the solution in a plastic bottle. standard solution a: transfer 10.0 ml of standard stock solution to a 500- ml volumetric flask, add 50 ml of 1 n hydrochloric acid, and dilute with water to volume. transfer 20.0 ml of this solution to a 200- ml volumetric flask, and dilute with water to volume. notethis solution contains 2 g/ml of magnesium. standard solution b: combine 5.0 ml of standard solution a and 4.0 ml of lanthanum solution, and dilute with water to 100.0 ml (0.1 g/ml). standard solution c: combine 10.0 ml of standard solution a and 4.0 ml of lanthanum solution, and dilute with water to 100.0 ml (0.2 g/ml). standard solution d: combine 15.0 ml of standard solution a and 4.0 ml of lanthanum solution, and dilute with water to 100.0 ml (0.3 g/ml). standard solution e: combine 20.0 ml of standard solution a and 4.0 ml of lanthanum solution, and dilute with water to 100.0 ml (0.4 g/ml). standard solution f: combine 25.0 ml of standard solution a and 4.0 ml of lanthanum solution, and dilute with water to 100.0 ml (0.5 g/ml). note concentrations of the standard solutions and the sample solution may be modified to fit the linear or working range of the instrument. when using instruments with a linear calibration graph, the number of standard solutions can be reduced. blank solution: transfer 4.0 ml of lanthanum solution to a 100- ml volumetric flask, and dilute with water to volume. sample solution: transfer 250 mg of esomeprazole magnesium to a 100- ml volumetric flask, add 20 ml of 1 n hydrochloric acid, swirl until dissolved, and dilute with water to volume. allow to stand for 30 min. transfer 10.0 ml of this solution to a 200- ml volumetric flask, and dilute with water to volume. transfer 10.0 ml of the solution to another 100- ml volumetric flask, add 4.0 ml of lanthanum solution, and dilute with water to volume. spectrometric conditions (see spectrophotometry and light- scattering 851 .) mode: atomic absorption spectrophotometer flame: airacetylene analytical wavelength: 285.2 nm analysis samples: standard solution b, standard solution c, standard solution d, standard solution e, standard solution f, blank solution, and sample solution determine the concentration, cs, in g/ml, of magnesium in the sample solution using the calibration graph. calculate the percentage of magnesium in the portion of esomeprazole magnesium taken: 页码，3 / 7 2 0 1 0 u s p c o f f i c i a l 5 / 1 / 1 1 - 7 / 3 1 / 1 1 u s p m o n o g r a p h s : e s o m e p r a z o l e . . . 2 0 1 1 - 5 - 4f i l e : / / c : c o m _ c a i s l a b s _ e b k d a t a v 3 4 2 9 0 u s p 3 4 n f 2 9 s 0 _ m 3 0 5 8 8 . h t m l result = (cs/cu) (100/(100 f) 100 acceptance criteria: 3.30%3.55%, on anhydrous basis impurities organic impurities procedure 1 solution a: 0.725 g of monobasic sodium phosphate and 4.472 g of anhydrous dibasic sodium phosphate in 300 ml of water, and dilute with water to 1000 ml. dilute 250 ml of this solution with water to 1000 ml. if necessary, adjust with phosphoric acid to a ph of 7.6. mobile phase: acetonitrile and solution a (11:29). noteto improve the resolution, the composition may be changed to 1:3, if necessary. system suitability solution: 1 mg of usp omeprazole rs and 1 mg of usp omeprazole related compound a rs in 25 ml of mobile phase. note omeprazole related compound a is omeprazole sulfone. sample solution: 4 mg of esomeprazole magnesium in 25 ml of mobile phase. noteprepare this solution fresh. chromatographic system (see chromatography 621 , system suitability.) mode: lc detector: uv 280 nm column: 4.0- mm 12.5- cm or a 4.6- mm 15- cm; 5- m packing l7. note alternatively, a 3.9- mm 15- cm column that contains 4- m packing l1 may be used. flow rate: 0.81 ml/min injection size: 50 l system suitability sample: system suitability solution notefor relative retention times, see impurity table 1. suitability requirements resolution: nlt 3 between omeprazole related compound a and omeprazole analysis sample: sample solution cs= = content of magnesium in the sample solution as calculated above (g/ml) cu= = concentration of esomeprazole magnesium in the sample solution (g/ml) f= = content of water in esomeprazole magnesium, as determined in specific tests, water determination (%) 页码，4 / 7 2 0 1 0 u s p c o f f i c i a l 5 / 1 / 1 1 - 7 / 3 1 / 1 1 u s p m o n o g r a p h s : e s o m e p r a z o l e . . . 2 0 1 1 - 5 - 4f i l e : / / c : c o m _ c a i s l a b s _ e b k d a t a v 3 4 2 9 0 u s p 3 4 n f 2 9 s 0 _ m 3 0 5 8 8 . h t m l record the chromatogram for at least 4.5 times the retention time of the omeprazole peak, and measure the peak responses. identify the impurities based on the retention times shown in impurity table 1. calculate the percentage of any individual impurity in the portion of esomeprazole magnesium taken: result = (ru/rt) 100 acceptance criteria individual impurities: see impurity table 1. total impurities: nmt 0.5% impurity table 1 procedure 2: enantiomeric purity solution a: mix 70 ml of 1 m monobasic sodium phosphate with 20 ml of 0.5 m dibasic sodium phosphate, and dilute with water to 1000 ml. dilute 250 ml of this solution with water to 1000 ml. diluent: mix 11 ml of 0.25 m tribasic sodium phosphate with 22 ml of 0.5 m dibasic sodium phosphate, and dilute with water to 1000 ml. mobile phase: acetonitrile and solution a (3:17) system suitability solution: 2 mg of usp omeprazole rs in 10 ml of diluent. dilute 1.0 ml of this solution with diluent to 50 ml. sample solution: 40 mg of esomeprazole magnesium in 5 ml of methanol, and dilute with diluent to 25 ml. dilute 1 ml of this solution with diluent to 50 ml. chromatographic system (see chromatography 621 , system suitability.) mode: lc detector: uv 302 nm ru= = peak response for each impurity rt= = sum of all peak responses name relative retention time acceptance criteria, nmt (%) omeprazole n- oxide a0.450.1 omeprazole sulfoneb (related compound a)0.80.2 any other individual impurities0.1 omeprazole1.0 a 4- methoxy- 2- (rs)- (5- methoxy- 1h- benzimidazol- 2- yl)sulfinylmethyl- 3,5- dimethylpyridine 1- oxide. b 5- methoxy- 2- (4- methoxy- 3,5- dimethylpyridin- 2- yl)methylsulfonyl- 1h- benzimidazole. 页码，5 / 7 2 0 1 0 u s p c o f f i c i a l 5 / 1 / 1 1 - 7 / 3 1 / 1 1 u s p m o n o g r a p h s : e s o m e p r a z o l e . . . 2 0 1 1 - 5 - 4f i l e : / / c : c o m _ c a i s l a b s _ e b k d a t a v 3 4 2 9 0 u s p 3 4 n f 2 9 s 0 _ m 3 0 5 8 8 . h t m l column: 4.0- mm 10- cm; packing l41 flow rate: 0.6 ml/min injection size: 20 l system suitability sample: system suitability solution suitability requirements resolution: nlt 3 between the enantiomer peaks. notethe elution order is the r- enantiomer, followed by the esomeprazole peak, which is the s- enantiomer. analysis sample: sample solution calculate the percentage of the r- enantiomer in the portion of esomeprazole magnesium taken: result = (ru/rs) 100 acceptance criteria: nmt 0.2% of the r- enantiomer specific tests water determination, method i 921 : 6.0%8.0% color of solution sample solution: 20 mg/ml of esomeprazole magnesium in methanol analysis: determine the absorbance of this solution at 440 nm, in 1- cm cells, using methanol as the blank. acceptance criteria: nmt 0.2 additional requirements packaging and storage: preserve in tight containers, protected from light. store at room temperature. usp reference standards 11 usp esomeprazole magnesium rs usp omeprazole rs usp omeprazole related compound a rs omeprazole sulfone, 5- methoxy- 2- (4-